Nanostructured delivery systems with improved leishmanicidal activity: a critical review

Figures & data

Table 1 Price per visceral leishmaniasis treatment

Compound	Treatment regimen (days)	Drug costa
L-AmpB 10 mg/kg	1	126
L-AmpB 20 mg/kg	2–4	252
AmpB deoxycholate 1 mg/kg	30	20
MF 100 mg/day	28	66–150
PM 15 mg/kg/day	21	15
SSG 20 mg/kg/day	30	56
MA 20 mg/kg/day	30	59
L-AmpB 5 mg/kg + MF 100 mg/day	8	88–110
L-AmpB 5 mg/kg + PM 15 mg/kg/day	11	79
MF 100 mg/kg + PM 15 mg/kg/day	10	30–61
(SSG 20 mg + PM 15 mg)/kg/day	17	44

Note:

a For a patient weighing 35 kg, cost in US dollars (January 2010).

Abbreviations: AmpB, amphotericin B; L-AmpB, liposomal AmpB; MA, meglumine antimonate; MF, miltefosine; PM, paromomycin; SSG, sodium stibogluconate.

Table 2 Principal characteristics of amphotericin delivery systems with the most advanced in vivo results available

Name	Class component	Targeting	Drug loading (%)	Size (nm)	In vitro data	Parasitemia load reduction (%)a	Pharmacokinetics/biodistribution	Acute toxicity	Reference standard	Reference	Publication date
AmBisome	Liposomes		10	60–70			+	+		^Citation191	On market
Fungizone	Micelles			220				−		^Citation192	On market
Kalsome10	Liposomes								Am	^Citation59
Lec–AmpB NP	Lipidic nanoparticles		0.24 mg/mL	200–300	+	–	+ Oral	−	F	^Citation69	2015
	Liposomes	Tuftsin	2	80	+	s 78 vs 65	−	−	F	^Citation71	2002
	MLV liposomes	Mannose	62 (EE)	2,000	+	79 vs 42	+	−	F	^Citation73	2011
	MLV liposomes	Cationic	65 (EE)	2,000	+	61 vs 42	+	−	F	^Citation73	2011
ICo-010	Nanoemulsion		nd	200–1,000	+	l 83 vs 48	− Oral	−	Am	^Citation75	2010
Bioral	Nanocochleates		14–16	nd	+	–	− Oral	−	F	^Citation83, ^Citation84	Phase I
	SLN	Chitosan	9	160	+	Immunomodulation	−	+	F, Am	^Citation87	2014
	SLN	Mannose	99 (EE)	200–700	+	l 95 vs 82 s 94 vs 69	+	+	F	^Citation90	2009
	PLGA NP		10	80–160	+	–	−	−	F, Am	^Citation97	2012
	PLGA LPNP	Stearylamine	9	150–250	+	s 89 vs 64	+	+	Am	^Citation102	2015
	PLGA	Mannose	6	70	+	–	+	−	F	^Citation103	2009
	PLGA	Mannan	0.58	180	+	l 50 vs 30 s 48 vs 22	−	−	F	^Citation105	2015
	PLGA	Lactoferrin	9	200	+	s 90 vs 70 Am, 60 F	+	+	F, Am	^Citation107	2015
	PLGA	mAb CD14	nd	25–30	+	s 93 vs 74	−	−	F	^Citation109	2015
	PLGA		6	180	+	–	+ Oral	−	F	^Citation53	2009
	Albumin NP		4	1,000	+	l 90 vs 60 s 90 vs 65	+	−	F	^Citation193	2004
	PLGA		28	1,600–1,900	+	l 76 vs 0 s 70 vs 0	−	−	F	^Citation194	2005
	Albumin		4	2,100	+	l 97 vs 0 s 97 vs 0	−	−	F	^Citation194	2005
	Polyanhydride		44	1,000	+	l <0 vs 0 s 66 vs 0	−	−	F	^Citation194	2005
Chitosan	Nanocapsules		10	160	+	s 86 vs 70 Am, 55 F	−	−	F, Am	^Citation120	2013
Chitosan	Nanocapsules	Mannose	9	200	+	s 90 vs 50	+	−	F	^Citation121	2015
PEC chitosan-chondroitin sulfate	Nanoparticles		11	136	+	–	−	−	AmpB	^Citation122	2014
L-Psomes	Chitosan stearic		26	340	+	s 65 vs 55 F, 65 vs 62 Am	−	−	F, Am	^Citation123	2014
L-Psomes	Chitosan stearic + alginate		22	300	+	s 70 vs 53	+	−	F	^Citation124	2015
Ca3(PO4)2	Nanoparticles		8–11	110–170	+	s 77 vs 72 Am	+	+	F, Am	^Citation145	2016
NIV			nd	230	+	s 79 vs 86 l 89 vs 99	−	−	Am	^Citation127	1997
NIV	Inhalation admin		nd	1,600	+	l 85 vs 90	−	−	Am	^Citation100	2012
HPMA prodrug	Polymer conjugate		27	–	+	l 47 vs 98	−	+	Am	^Citation150	2009
HPMA prodrug	Polymer conjugate	Mannose	10	–		l 35 vs 98	−	+	Am	^Citation150	2009

Note:

a Parasitemia load reduction in l or s is expressed as % VL removal of nanosystems vs reference drug that is Am, F, and AmpB.

Abbreviations: Am, AmBisome; AmpB, Amphotericin B; EE, encapsulation efficiency; F, Fungizone; HPMA, N-(2-hydroxypropyl)methacrylamide; l, liver; Lec, lecithin; LPNP, lipid–polymer hybrid nanoparticle; L-Psomes, lipo-polymerosomes; MLV, multilamellar vesicle; nd, not determined; NIV, nonionic surfactant vesicles; NP, nanoparticle; PEC, Polyelectrolyte complex; PLGA, poly(lactide-co-glycolide); s, spleen; SLN, solid lipid nanoparticle; VL, visceral leishmaniasis.

Figure 1 Schematic representation of different classes of antileishmanial nanometric delivery systems.

Note: The character size (also bold type) evidences the number of publications related to each system.

Abbreviations: PCL, poly(caprolactone); PGA, poly(glycolic acid); PLA, poly(lactic acid); PLGA, poly(lactide-co-glycolide).

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